It is the purpose of this project to study the mode of action and the pharmacology of antitumor agents of the ansa macrolide class. Attention is presently focused on the plant product maytansine and its naturally occurring and semisynthetic derivatives. Maytansine was found to produce metaphase arrest in a manner similar to that seen with the Vinca alkaloids, and to impair microtubule formation in cultured L1210 cells. Topics of current interest are a) the nature of the maytansine binding site; b) a comparison of the binding properties of maytansine with those of its structural analogs; and c) bioassay methods for maytansine. BIBLIOGRAPHIC REFERENCES: Adamson, R.H., Zaharevitz, D.W., and Johns, D.G.: Enhancement of the biological activity of adenosine analogs by the adenosine deaminase inhibitor 2'deoxycoformycin. Pharmacology 15: 84-89, 1977. Chabner, B.A. and Johns, D.G.: Folate antagonists. In Becker, F.F. (Ed.): Cancer, A Comprehensive Treatise, Vol. 5 New York, Plenum Press, 1977, pp. 363-377.